A Two Week Study to Assess the Tolerability of AZD9668 in Chronic Obstructive Pulmonary Disease (COPD) Patients

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00703391
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arms: 2
• Duration (Months): 3
• Patients Per Site Per Month: 6

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the tolerability (effect of drug on body) and pharmacokinetics (effect of body on drug) of AZD9668 in patients with mild to moderate COPD

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease (COPD)	Drug: AZD9668; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: A 2-week, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Tolerability and Pharmacokinetics of Orally Administered AZD9668 in Patients With COPD
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Active Treatment	Drug: AZD9668; 30mg oral tablets twice daily (bid) for 14 days
Placebo Comparator: 2 Placebo Treatment	Drug: Placebo; Matched placebo to 30mg oral tablet twice daily (bid) for 14 days

Outcome Measures

Primary Outcome Measures

1. Alanine Aminotransferase (ALT) [Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)]

   ALT level greater than 3 times the upper limit of normal

2. Aspartate Aminotransferase (AST) [Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)]

   AST level greater than 3 times the upper limit of normal

3. Creatine Kinase (CK) [Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)]

   Change from baseline to Day 14

4. Total Bilirubin [Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)]

   Change from baseline to Day 14

5. Creatinine [Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)]

   Creatinine level greater than the upper limit of normal

6. Haemoglobin (Hb) [Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)]

   Change from baseline to Day 14

7. Reticulocytes [Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)]

   Change from baseline to Day 14

8. Leucocytes [Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)]

   Change from baseline to Day 14

9. QTcF (QT Interval Corrected for Heart Rate by Fridericia's Method) [Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)]

   QTcF interval greater than 450 ms

10. QTcF [Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)]

    QTcF change from baseline greater than 60 ms

11. FEV1 (Forced Expiratory Volume in the First Second) [Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)]

    Change from baseline to Day 14

12. Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose (AUC(0-12)) [Pre-dose on day -1 to day 15 (end of dosing)]

    AUC(0-12) following 14 days' dosing

13. Observed Peak or Maximum Plasma Concentration Following Drug Administration (Cmax) [Pre-dose on day -1 to day 15 (end of dosing)]

    Cmax following 14 days' dosing

14. Time to Reach Observed Peak or Maximum Concentration Following Oral Drug Administration (Tmax) [Pre-dose on day -1 to day 15 (end of dosing)]

    tmax following 14 days' dosing

15. Terminal Half-life of Drug in Plasma (t1/2) [Pre-dose on day -1 to day 15 (end of dosing)]

    t1/2 following 14 days' dosing

16. Renal Clearance of Drug From Plasma (CLR) [Pre-dose on day -1 to day 15 (end of dosing)]

    CLR following 14 days' dosing

Secondary Outcome Measures

1. Sputum Absolute Neutrophil Count [Pre-dose day -1 to post-dose on day 14]

   Change from baseline to Day 14 in absolute neutrophil count

2. Sputum Differential Neutrophil Count [Pre-dose day -1 to post-dose on day 14]

   Change from baseline to Day 14 in percentage neutrophil count

3. AZD9668 Sputum Concentrations [Pre-dose day -1 to post-dose on day 14]

4. Quantitative Sputum Bacteriology [Pre-dose day -1 to post-dose on day 15]

   Number of patients with an increase in bacteriological count from Day -1 to Day 15

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Mild to moderate COPD

• Smokers or ex-smokers

• post-menopausal females

Exclusion Criteria:

• Past history or current evidence of clinically significant heart disease

• Lung disease other than COPD

• Treatment with systemic steroids within 8 weeks of study visit 2

• Treatment with antibiotics within 4 weeks of study visit 1 or study visit 2

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Berlin		Germany

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Kristina Panke, Parexel International GmbhH (CRO)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00703391
• Other Study ID Numbers: D0520C00002
• First Posted: Jun 23, 2008
• Last Update Posted: Jan 26, 2012
• Last Verified: Jan 1, 2012

• Keywords provided by AstraZeneca: Chronic; obstructive; pulmonary; lung; respiratory disease; tolerability; placebo-controlled; pharmacokinetics; COPD
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive

Study Results

Participant Flow

Recruitment Details	First patient enrolled: 11 June 2008. Last patient completed: 09 October 2008. Single-centre study performed at a Clinical Pharmacology Unit

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Period Title: Overall Study
STARTED	12	6
COMPLETED	12	6
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	AZD9668	Placebo	Total
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days	Total of all reporting groups
Overall Participants	12	6	18
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	57.6	52.8	56
Sex: Female, Male (Count of Participants)
Female	3 25%	2 33.3%	5 27.8%
Male	9 75%	4 66.7%	13 72.2%

Outcome Measures

1. Primary Outcome

Title	Alanine Aminotransferase (ALT)
Description	ALT level greater than 3 times the upper limit of normal
Time Frame	Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	12	6
Number [Participants]	0 0%	0 0%

2. Primary Outcome

Title	Aspartate Aminotransferase (AST)
Description	AST level greater than 3 times the upper limit of normal
Time Frame	Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	12	6
Number [Participants]	0 0%	0 0%

3. Primary Outcome

Title	Creatine Kinase (CK)
Description	Change from baseline to Day 14
Time Frame	Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	12	6
Mean (Standard Deviation) [IU/L]	2.57 (19.260)	-69.57 (141.383)

4. Primary Outcome

Title	Total Bilirubin
Description	Change from baseline to Day 14
Time Frame	Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	12	6
Mean (Standard Deviation) [micromol/L]	0.11 (2.124)	-0.28 (2.563)

5. Primary Outcome

Title	Creatinine
Description	Creatinine level greater than the upper limit of normal
Time Frame	Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	12	6
Number [Participants]	1 8.3%	1 16.7%

6. Primary Outcome

Title	Haemoglobin (Hb)
Description	Change from baseline to Day 14
Time Frame	Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	12	6
Mean (Standard Deviation) [g/L]	-2.0 (4.73)	-0.2 (6.18)

7. Primary Outcome

Title	Reticulocytes
Description	Change from baseline to Day 14
Time Frame	Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	12	6
Mean (Standard Deviation) [relative particle count (%)]	-0.15 (2.851)	1.73 (1.605)

8. Primary Outcome

Title	Leucocytes
Description	Change from baseline to Day 14
Time Frame	Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	12	6
Mean (Standard Deviation) [10**9/L]	-0.001 (0.8816)	0.265 (0.4657)

9. Primary Outcome

Title	QTcF (QT Interval Corrected for Heart Rate by Fridericia's Method)
Description	QTcF interval greater than 450 ms
Time Frame	Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	12	6
Number [Participants]	0 0%	0 0%

10. Primary Outcome

Title	QTcF
Description	QTcF change from baseline greater than 60 ms
Time Frame	Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	12	6
Number [Participants]	0 0%	0 0%

11. Secondary Outcome

Title	Sputum Absolute Neutrophil Count
Description	Change from baseline to Day 14 in absolute neutrophil count
Time Frame	Pre-dose day -1 to post-dose on day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	7	4
Median (Full Range) [10**9/L]	-0.4890	-2.5645

12. Secondary Outcome

Title	Sputum Differential Neutrophil Count
Description	Change from baseline to Day 14 in percentage neutrophil count
Time Frame	Pre-dose day -1 to post-dose on day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	12	6
Median (Full Range) [Percentage]	1.8	-4.25

13. Secondary Outcome

Title	AZD9668 Sputum Concentrations
Time Frame	Pre-dose day -1 to post-dose on day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	11	0
Geometric Mean (Full Range) [nM]	41.7

14. Secondary Outcome

Title	Quantitative Sputum Bacteriology
Description	Number of patients with an increase in bacteriological count from Day -1 to Day 15
Time Frame	Pre-dose day -1 to post-dose on day 15

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	12	6
Number [Participants]	3 25%	2 33.3%

15. Primary Outcome

Title	FEV1 (Forced Expiratory Volume in the First Second)
Description	Change from baseline to Day 14
Time Frame	Throughout the duration of the study (pre-dose, cmax, steady state, end of dosing and post dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	12	6
Mean (Standard Deviation) [L]	0.039 (0.2173)	-0.110 (0.3043)

16. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose (AUC(0-12))
Description	AUC(0-12) following 14 days' dosing
Time Frame	Pre-dose on day -1 to day 15 (end of dosing)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	12	0
Geometric Mean (Full Range) [nM.h]	7560

17. Primary Outcome

Title	Observed Peak or Maximum Plasma Concentration Following Drug Administration (Cmax)
Description	Cmax following 14 days' dosing
Time Frame	Pre-dose on day -1 to day 15 (end of dosing)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	12	0
Geometric Mean (Full Range) [nM]	1420

18. Primary Outcome

Title	Time to Reach Observed Peak or Maximum Concentration Following Oral Drug Administration (Tmax)
Description	tmax following 14 days' dosing
Time Frame	Pre-dose on day -1 to day 15 (end of dosing)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	12	0
Median (Full Range) [hours]	1.01

19. Primary Outcome

Title	Terminal Half-life of Drug in Plasma (t1/2)
Description	t1/2 following 14 days' dosing
Time Frame	Pre-dose on day -1 to day 15 (end of dosing)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	12	0
Median (Full Range) [hours]	5.89

20. Primary Outcome

Title	Renal Clearance of Drug From Plasma (CLR)
Description	CLR following 14 days' dosing
Time Frame	Pre-dose on day -1 to day 15 (end of dosing)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZD9668	Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days	Matched placebo tablets twice daily (bid) for 14 days
Measure Participants	12	0
Geometric Mean (Full Range) [L/h]	6.13

Adverse Events

Arm/Group Title	AZD9668		Placebo
Arm/Group Description	AZD9668 2x30mg oral tablets twice daily (bid) for 14 days		Matched placebo tablets twice daily (bid) for 14 days
All Cause Mortality
	AZD9668		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	AZD9668		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	AZD9668		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/ (NaN)		4/ (NaN)
Cardiac disorders
Palpitations	1/12 (8.3%)		0/6 (0%)
Ear and labyrinth disorders
Back pain	2/12 (16.7%)		0/6 (0%)
Gastrointestinal disorders
Diarrhoea	1/12 (8.3%)		0/6 (0%)
Dyspepsia	0/12 (0%)		1/6 (16.7%)
Nausea	1/12 (8.3%)		0/6 (0%)
Vomiting	1/12 (8.3%)		0/6 (0%)
General disorders
Chest discomfort	1/12 (8.3%)		0/6 (0%)
Fatigue	0/12 (0%)		1/6 (16.7%)
Infections and infestations
Respiratory tract infection	1/12 (8.3%)		0/6 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	1/12 (8.3%)		0/6 (0%)
Nervous system disorders
Headache	1/12 (8.3%)		4/6 (66.7%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/12 (8.3%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.